Ultrasonic diagnosis allows to display in real time how the heart beats or the fetus moves, by simply bringing an ultrasonic probe into contact with the body surface. This technique is highly safe, and hence allows repetitive examination. Furthermore, this system is smaller in size than other diagnostic apparatuses such as X-ray, CT, and MRI apparatuses and can be moved to the bedside to be easily and conveniently used for examination. In addition, ultrasonic diagnostic apparatuses vary in type depending on the functions which they have. Some compact apparatuses which have already been developed are small enough to be carried with one hand, and ultrasonic diagnosis is free from the influence of radiation exposure unlike diagnosis using X-rays. Therefore, such ultrasonic diagnostic apparatuses can be used in obstetric treatment, treatment at home, and the like.
Recently, intravenous-type ultrasonic contrast media (to be simply referred to as contrast media hereinafter) have been commercialized, and a “contrast echo method” has been practiced. This technique aims at hemodynamics evaluation upon enhancement of a blood flow signal by injecting an ultrasonic contrast medium through a vein in, for example, cardiac and hepatic examinations. Many contrast media function by using microbubbles as reflection sources. For example, a second-generation ultrasonic contrast medium called Sonazoid® which has recently been released in Japan comprises microbubbles each covered with a phospholipid film and containing a perfluorobutane gas. It has become possible to stably observe how a contrast medium refluxes, using ultrasonic transmission waves with an amplitude small enough not to destroy microbubbles.
Scanning a diagnostic region (e.g., liver cancer) after the administration of a contrast medium allows to observe increases and decreases in signal intensity from the inflow of a contrast medium, which circulates on a blood flow, to the outflow of the contrast medium. Studies have been made to enable benignancy/malignancy differential diagnosis of a tumoral lesion or diagnosis of a “diffuse” disease or the like based on such differences in temporal changes in signal intensity.
In general, such temporal changes in signal intensity need to be recorded or interpreted as a moving image unlike simple morphological information. This generally leads to a long time required for interpretation. Under the circumstance, there has been proposed a technique of mapping the inflow time information of a contrast medium to be generally observed in moving images onto a single still image (see Jpn. Pat. Appln. KOKAI Publication No. 2001-269341, and Jpn. Pat. Appln. KOKAI Publication No. 2004-321688). Such a technique expresses, with different hues, the differences between the peak times of signals based on a contrast medium and allows to recognize at a glance the inflow time at each position within a diagnostic slice.
In tumor blood vessels which run in a complicated manner as compared with normal blood vessels, a phenomenon is observed, in which bubbles have nowhere to go and become stagnant or reflux after stagnation (see R. K. Jain, “Normalization of Tumor Vasculature: An Emerging Concept in Antiangiogenetic Therapy”, Science, Vol. 307, pp. 58-62, January 2005). In practice, when performing contrast medium ultrasonic observation using a tumor mouse, the behavior of bubbles like that described above is observed in tumor blood vessels. If it is possible to evaluate the behavior of bubbles with contrast-enhanced ultrasonic waves which enable biological imaging, there is a possibility that this technique can be applied to the evaluation of abnormality of tumor blood vessels.
It has been confirmed by histopathological observation that an antiangiogenic agent (anticancer agent) which has currently been clinically tested fragments/confines tumor blood vessels by destroying blood vessels that nourish the tumor (see M. Yamazaki, et al., “Sonic hedgehog derived from human pancreatic cancer cells augments angiogenic function of endothelial progenitor cells”, Cancer Science, Vol. 99(6), pp. 1131-1138). If it is possible to visualize and quantify, with contrast-enhanced ultrasonic waves, the manner of how bubbles become stagnant in blood vessels fragmented by the antiangiogenic agent, this technique can be expected to be applied to treatment effect determination.
However, mapping of contrast medium inflow times (arrival times) using a conventional ultrasonic diagnostic apparatus cannot express characteristics after the arrival of the contrast medium. For example, it is not possible to discriminate between, for example, a state in which a contrast medium is continuously flowing into a given area and new microbubbles (to be simply referred to as bubbles hereinafter) are replacing old bubbles and a state in which bubbles that have flowed into the area are stagnant.
Note that, for example, the technique disclosed in Jpn. Pat. Appln. KOKAI Publication No. 2001-269341 displays contrast medium inflow information (e.g., arrival times) in an ultrasonic scanning slice by color mapping with reference to a given time, and hence allows to observe, in an entire image, how a contrast medium flows into each area. However, this technique does not allow sufficient evaluation of the stagnant state of bubbles after the arrival of the contrast medium at each area. In addition, the technique disclosed in Jpn. Pat. Appln. KOKAI Publication No. 2004-321688 can present the information of arrival times by performing more precise computation based on a logical model of the reflux of microcirculatory blood flows. However, even this technique cannot sufficiently evaluate the stagnant state of bubbles after the arrival of a contrast medium at each area.